CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability

Mehta, Suresh L.; Chokkalla, Anil K; Bathula, Saivenkateshkomal; Arruri, Vijay Kumar; Chelluboina, Bharath; Vemuganti, Raghu

doi:10.1016/j.omtn.2022.11.022

Cited by 19 publications

(13 citation statements)

References 44 publications

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“…Furthermore, at 7 dpi, miR-7 inducible KO mice showed an exaggerated ischemic lesion size compared to WT animals, reinforcing the idea of a role of miR-7 in regulating ischemic damage. Moreover, our data is in line with literature showing that the levels of miR-7 are downregulated at early timepoints in ischemic stroke and that upregulation in miR-7 is necessary for stroke recovery 45 . These data together propose a model in which ciRS-7 and Cyrano regulate miR-7 and possibly influence its upregulation acting as a "buffering" system.…”

Section: Discussionsupporting

confidence: 92%

ciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signaling

Scoyni

Sitnikova

Giudice

et al. 2023

Preprint

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Brain functionality resides on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7, the microRNA miR-7 and the long non-coding RNA Cyrano. However, very little is known on how this network regulates stress responses in neurodegeneration. Here we describe ischemia induced alterations in the ncRNA network both in vitro and in vivo and in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression upon ischemic insults. Mice lacking ciRS-7 show reduced lesion size and motor impairment, whilst the absence of miR-7 alone leads to an increase in the ischemia induced neuronal death. Moreover, miR-7 levels in pyramidal excitatory neurons regulate dendrite morphology and glutamatergic signaling suggesting a potential molecular link to the in vivo phenotype. Our data reveal a new endogenous mechanism by which ciRS-7 and miR-7 regulate the outcome of ischemic stroke and shed new light into the pathophysiological roles of intracellular networks of non-coding RNAs in the brain.

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Section: Discussionsupporting

confidence: 92%

ciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signaling

Scoyni

Sitnikova

Giudice

et al. 2023

Preprint

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“…Animals that showed no signs of neurological deficits during the acute phase after MCAO and/or showed a hemorrhage after euthanasia were excluded from the study. 6,8,12,24,25…”

Section: Methodsmentioning

confidence: 99%

“…Focal ischemia was induced by transient MCAO using a silicone-coated nylon monofilament (4-0 for rats and 6-0 for mice, Doccol, USA) under isoflurane anesthesia, as described earlier. 6,8,9,12,[23][24][25] MCA was occluded for 60 min in SHR rats and C57BL/6 mice, 90 min for FosDT þ/þ /FosDT À/À rats, and 35 min for db/db mice. 6,8,24 Sham controls underwent the same surgical procedure, except for MCAO.…”

Section: Focal Cerebral Ischemiamentioning

confidence: 99%

“…Animals that showed no signs of neurological deficits during the acute phase after MCAO and/or showed a hemorrhage after euthanasia were excluded from the study. 6,8,12,24,25 siRNA injections Rats and mice were injected with a cocktail of 3 FosDT siRNAs or nontargeting negative control siRNA (Cat # 4390844; Life Technologies, USA) at either 30 min, 2 h, or 3.5 h of reperfusion following transient MCAO. 6,9,25 The sequences of the FosDT siRNAs used for rats were (5' to 3'): GGT TCA TTA TTG GAA TTA Att (sense) and TTA ATT CCA ATA ATG AAC Cca (antisense); CCA TGT TCA TTG TCA TGT Att (sense) and TAC ATG ACA ATG AAC ATG Gac (antisense); GAC CAAT ATT AAA CTA AGA tt (sense) and TCT TAG TTT AAT ATT GGT Cat (antisense).…”

Section: Focal Cerebral Ischemiamentioning

confidence: 99%

“…2 We recently showed that stroke induces extensive spatiotemporal changes in the heterogeneous network of protein-coding RNAs and noncoding RNAs (ncRNAs) that significantly alter the long-term neurologic function and present a unique opportunity for therapeutic targeting. [3][4][5][6][7][8][9][10][11][12] Several ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been recently shown to modulate post-stroke secondary brain damage. [6][7][8][9]11,13 This is corroborated by the several RNA-based therapies tested in clinical settings over the past decade, some of which have received FDA approval to treat a range of disorders, including those related to the CNS.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Post-stroke brain can be protected by modulating the lncRNA FosDT

Mehta,

Chelluboina,

Morris-Blanco

et al. 2023

J Cereb Blood Flow Metab

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We previously showed that knockdown or deletion of Fos downstream transcript (FosDT; a stroke-induced brain-specific long noncoding RNA) is neuroprotective. We presently tested the therapeutic potential of FosDT siRNA in rodents subjected to transient middle cerebral artery occlusion (MCAO) using the Stroke Treatment Academic Industry Roundtable criteria, including sex, age, species, and comorbidity. FosDT siRNA (IV) given at 30 min of reperfusion significantly improved motor function recovery (rotarod test, beam walk test, and adhesive removal test) and reduced infarct size in adult and aged spontaneously hypertensive rats of both sexes. FosDT siRNA administered in a delayed fashion (3.5 h of reperfusion following 1 h transient MCAO) also significantly improved motor function recovery and decreased infarct volume. Furthermore, FosDT siRNA enhanced post-stroke functional recovery in normal and diabetic mice. Mechanistically, FosDT triggered post-ischemic neuronal damage via the transcription factor REST as REST siRNA mitigated the enhanced functional outcome in FosDT−/− rats. Additionally, NF-κB regulated FosDT expression as NF-κB inhibitor BAY 11-7082 significantly decreased post-ischemic FosDT induction. Thus, FosDT is a promising target with a favorable therapeutic window to mitigate secondary brain damage and facilitate recovery after stroke regardless of sex, age, species, and comorbidity.

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Stoichiometry of long noncoding RNA interactions with other RNAs: Insights from OIP5‐AS1

Yang,

Tsitsipatis,

Gorospe

2024

WIREs RNA

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Long noncoding (lnc)RNAs modulate gene expression programs in a range of developmental processes in different organs. In skeletal muscle, lncRNAs have been implicated in myogenesis, the process whereby muscle precursor cells form muscle fibers during embryonic development and regenerate muscle fibers in the adult. Here, we discuss OIP5‐AS1, a lncRNA that is highly expressed in skeletal muscle and is capable of coordinating protein expression programs during myogenesis. Given that several myogenic functions of OIP5‐AS1 involve interactions with MEF2C mRNA and with the microRNA miR‐7, it was critical to carefully evaluate the precise levels of OIP5‐AS1 during myogenesis. We discuss the approaches used to examine lncRNA copy number using OIP5‐AS1 as an example, focusing on quantification by quantitative PCR analysis with reference to nucleic acids of known abundance, by droplet digital (dd)PCR measurement, and by microscopic visualization of individual lncRNAs in cells. We discuss considerations of RNA stoichiometry in light of developmental processes in which lncRNAs are implicated.This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability

Cited by 19 publications

References 44 publications

ciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signaling

ciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signaling

Post-stroke brain can be protected by modulating the lncRNA FosDT

Stoichiometry of long noncoding RNA interactions with other RNAs: Insights from OIP5‐AS1

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